CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
artículos
Título:
Postnatal metformin treatment alters rat Sertoli cell proliferation and daily sperm production
Autor/es:
ELIANA HERMINIA PELLIZZARI; VANINA GABRIELA DA ROS; MARIA FERNANDA RIERA; GUSTAVO MARCELO RINDONE; MARIA DEL CARMEN CAMBEROS; MARIANO GABRIEL BUFFONE; AGOSTINA GORGA; MARIA NOEL GALARDO; SILVINA BEATRIZ MERONI
Revista:
Andrology
Editorial:
wiley
Referencias:
Lugar: New Yersey; Año: 2021 vol. 2021 p. 965 - 976
ISSN:
2047-2927
Resumen:
Background: The direct correlation between Sertoli cell number and sperm production capacity highlights the importance of deciphering external factors that modify Sertoli cell proliferation. A growing body of evidence in vitro suggests that metformin, the main pharmacological agent for type 2 diabetes treatment in children, exerts antiproliferative effects on Sertoli cells. Objective: the aims of this study were to investigate the effect of metformin administration during postnatal period on Sertoli cell proliferation and on cell cycle regulators expression and analyze the impact of this treatment on the sperm production capacity in adulthood. Material and Methods: Sprague Dawley rat pups were randomly divided into two groups: MET (receiving daily 200 mg/kg metformin, from Pnd3 to Pnd7 inclusive) and control ( receiving vehicle). BrdU incorporation was measured to assess proliferation. Gene expression analyses were performed in Sertoli cells isolated from animals of both groups. Daily sperm production and sperm parameters were measured in adult male rats (Pnd90) that received neonatal treatment. Results: MET group exhibited a significant decrease in BrdU incorporation in Sertoli cells. Concordantly, MET goup showed a reduction in cyclin D1 and E2 expression and an increase in p21 expression in Sertoli cells. In addition, metformin-treated animals displayed lower values of daily sperm production on Pnd90. Discussion and Conclusion: These results suggest that metformin treatment may lead to a decrease in Sertoli cell proliferation, a concomitant altered expression of cell cycle regulators and ultimately, a reduction in daily sperm production in adult animals.